Maysinger D, Herrera-Marschitz M, Carlsson A, Garofalo L, Cuello A C, Ungerstedt U
Department of Pharmacology and Therapeutics, McGill University, Montreal, Canada.
Brain Res. 1988 Oct 4;461(2):355-60. doi: 10.1016/0006-8993(88)90267-3.
Striatal and cortical extracellular acetylcholine (ACh) and choline (Ch) levels were determined in samples collected under in vivo conditions using microdialysis in normal (naive) and decorticated rats treated with saline or the monoganglioside GM1. ACh and Ch were assayed using a sensitive high performance liquid chromatography technique coupled to a postcolumn reactor with immobilized enzymes. Picomole amounts of ACh could be measured in the presence of an acetylcholinesterase inhibitor (neostigmine) in the microdialysis perfusion medium (striatal ACh = 0.2-0.4 microM; cortical ACh = 0.03-0.04 microM). Ch was detected both in the presence and in the absence of neostigmine (striatal Ch = 0.5-0.6 microM; cortical Ch = 0.6-2 microM). ACh, but not Ch, was strongly stimulated by 100 mM of KCl included in the perfusion medium. Decortication produced by devascularization did not significantly modify the cortical or striatal basal levels of ACh. However, in the cortex, KCl produced a higher ACh stimulation in the GM1-treated than in the saline-treated decorticated or naive rats. The present results indicate that GM1-treatment increases the ability of cortical cholinergic terminals to release ACh and support the idea that trophic factors such as monoganglioside GM1 can promote recovery following injuries of the central nervous system.
使用微透析技术,在体内条件下,测定正常(未处理)和去皮质大鼠(分别用生理盐水或单唾液酸四己糖神经节苷脂GM1处理)纹状体和皮质细胞外乙酰胆碱(ACh)及胆碱(Ch)水平。采用灵敏的高效液相色谱技术结合固定化酶的柱后反应器测定ACh和Ch。在微透析灌注介质中加入乙酰胆碱酯酶抑制剂(新斯的明)后,可检测到皮摩尔量的ACh(纹状体ACh = 0.2 - 0.4微摩尔/升;皮质ACh = 0.03 - 0.04微摩尔/升)。无论有无新斯的明,均可检测到Ch(纹状体Ch = 0.5 - 0.6微摩尔/升;皮质Ch = 0.6 - 2微摩尔/升)。灌注介质中加入100毫摩尔/升氯化钾可强烈刺激ACh,但对Ch无刺激作用。去血管化造成的去皮质状态并未显著改变皮质或纹状体ACh的基础水平。然而,在皮质中,氯化钾对GM1处理组大鼠的ACh刺激作用高于生理盐水处理的去皮质大鼠或正常大鼠。目前的结果表明,GM1处理可增强皮质胆碱能终末释放ACh的能力,并支持如下观点:诸如单唾液酸四己糖神经节苷脂GM1等营养因子可促进中枢神经系统损伤后的恢复。